All ETDs from UAB

Advisory Committee Chair

John F Kearney

Advisory Committee Members

David E Briles

Peter D Burrows

Christopher A Klug

Harry W Schroeder

Document Type

Dissertation

Date of Award

2010

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Mammalian antimicrobial peptides, including cathelicidins and defensins, play an important role in host defense via direct antimicrobial activity as well as immune regula-tion. The cathelin-related antimicrobial peptide (mCRAMP) is the only identified mouse cathelicidin and the orthologue of human LL-37. We show that all mouse B cell subsets, including follicular, marginal zone, B1a, and B1b cells, as well as CD4+ and CD8+ T cells produce mCRAMP directly ex vivo. In addition, mCRAMP-deficient B cells produced less IgG1 antibody in vitro in response to CD40L or LPS plus IL-4 when compared to WT B cells. The addition of recombinant mCRAMP at the time of mCRAMP-deficient B cell activation restored the level of IgG1 production to WT levels. mCRAMP-deficiency had no effect on proliferation, survival, or class switch recombina-tion, but resulted in a decrease in the amount of IgG1 mRNA. Surprisingly, mCRAMP-deficient mice immunized with TNP-OVA absorbed in Alum resulted in an enhanced TNP-specific IgG1 response when compared to WT B6 mice. ELISpot and PCR analysis revealed increased numbers of TNP-specific IgG1-secreting splenic B cells and increased CD4+ T cell IL-4 expression in mCRAMP-deficient mice. Taken together, B cells express and respond to mCRAMP positively in vitro while in vivo mCRAMP appears to also indirectly regulate B cell antibody production through regulation of T cell cytokine production.

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